On August 7, 2012, the Wall Street Journal posted an opinion piece entitled, “The FDA Wants to Regulate Your Cells”. In this article, the authors cite a decision 2 weeks ago in US District Court where the FDA had sued Regenerative Sciences, LLC, to cease providing stem-cell based treatments due to lack of marketing approval. The US District Court agreed with the FDA in this litigation.
In the United States, human tissue products are generally exempt from pre-market review by the FDA, provided they meet certain requirements. One of these requirements is that the tissues be “minimally manipulated”. Examples of human tissue that meets the “minimally manipulated” standard include organ transplants, blood transplants, allograft bone processed to remove lipids and cells, bone demineralized via acid treatment, and production of autologous platelet rich plasma (PRP) using a centrifuge for bed-side treatment. As such, all of these treatments are exempt from FDA pre-market review, except the centrifuge that produces the PRP.
However, the process used by Regenerative Sciences is described as follows:
“This procedure, called the RegenexxTM procedure, is used to treat certain orthopedic conditions, such as osteoarthritis, nonhealing bone fractures, avascular necrosis and bulging lumbar discs. In this procedure, the physician takes bone marrow from the patient’s hip or synovial fluid from the patient’s knee, as well as blood from the patient, and transports these materials to a nearby laboratory facility.
At this facility, mesenchymal stem cells are isolated from the bone marrow or synovial fluid and expanded in culture for two to three weeks using growth factors from the patient’s blood, as well as other chemical reagents. The cells are then combined with drug products, such as doxycycline, which have been previously approved by the FDA, and are then transported back to the clinic for injection into the patient.”
The district court sided with the FDA in deciding that process Regenerative Sciences utilized for processing the cells fell beyond the scope of “minimal manipulation”.
However, FDA’s view that these processing methods fall beyond the scope of “minimal manipulation” is not new. Genzyme’s Carticel, FDA approved under a Biologics Licensing Application (BLA) since 1997, is a procedure similar to the one outlined by Regenerative Sciences. Carticel is produced by isolating a small portion of a patient’s knee cartilage, from which the patient’s cells are isolated, expanded in cell culture, and re-injected into the patient.
In particular, the expansion of cells, which involves the addition of many reagents and growth factors in a sterile environment, is the key step that takes the production process beyond minimal manipulation. Many chemical entities are added to stimulate the cells to divide and grow to obtain enough cells for therapeutic success. These processes, as demonstrated by laboratory science, can change the nature of the cells such that they are not necessarily the same as the ones removed from the patient. While these changes could be beneficial in some circumstances (such as increased ability to repair damaged tissues in the body), there is inherent risk that the cells could cause an adverse reaction in the patient due to these changes to the cells. In FDA’s view, these treatments should be held to the same standards of safety and effectiveness as drugs and medical devices prior to use.
The WSJ article authors state:
“Federal regulators have stretched that definition to the point where a reasonable limit no longer exists. The law provided a clear impediment to unrestrained exercise of FDA authority. Something needed to be an “article”—not a medical procedure—in order to become a drug. The constraint that a drug needed to be a “thing” has been read out of the law by FDA, and the district court appears to have accepted that position.
If human cells processed by the Colorado doctors are “drugs” under federal law, even when these cells are returned to the same patient who donated them, there may be little to prevent the FDA from imposing its drug-approval requirements on any cell-based procedure.”
The authors’ inferences that the FDA is ever-stretching its boundaries of its review and that they can impose requirements on any cell-based procedure are misleading. As demonstrated by the Carticel example, this view by the FDA of cultured cells as being medical products, even if sourced from a patient’s own cells, is a 15 year old precedent. Furthermore, regulations prevent the FDA from reviewing many types of cellular procedures involving a patient’s own cells, provided they meet the “minimal manipulation” standard. Regulatory precedent has demonstrated that procedures involving separation of cells via centrifugation, simple mixing of cells (as in in vitro fertilization), and implantation without culture of these cells clearly fall within the boundaries of minimal manipulation.
In its current view, the FDA requires rigorous non-clinical and clinical data to determine the safety and effectiveness of these cellular-based treatments. While stem cell treatments and other cell-based treatments can provide exciting advances in the practice of medicine, the safety and effectiveness of these treatments have yet to be determined and successful results from isolated case reports should be viewed with scrutiny.